Download Two types of hormones

Announcements
• Today
– Signaling pathways and 2nd messengers
– Pituitary gland
– Course evaluations
Two types of hormones
• Lipid Soluble
– Steroid hormones (estrogen, testosterone)
– Thyroid hormones
• Lipid Insoluble
– Peptides and Proteins (insulin)
– Catecholamines (adrenalin)
Two types of hormones
1. Lipid-soluble
Carrier molecule
Hormone molecule
Cytoplasmic receptor
Nuclear receptor
Transcription &
Translation
long lasting effects
Nucleus
Two types of hormones
2. Lipid-insoluble
Hormone molecule
Plasma membrane receptor
Second Messenger
Effector Protein
Cellular effects
Signal Transduction
Signal
Reception, Transduction
Amplification
Second Messengers
Regulators
Specific Effectors
Cellular Response
Types of Second Messengers
• Cyclic nucleotides
– cAMP, cGMP
• Inositol phospholipid
– Inositol 1,4,5 triphosphate (IP3)
– 1,2-diacylglycerol (DAG)
• Calcium ions (Ca++)
cAMP / Protein Kinase A Pathway
Ri
Rs
Adenylate
Cyclase
Gs
Gi
stimulates
ATP
cAMP
Protein Kinase A
Ion
Channels
Membrane
Pumps
Metabolic
Enzymes
inhibits
cAMP / Protein Kinase A Pathway
Ri
Rs
Adenylate
Cyclase
Gs
ATP
Gi
cAMP
Regulatory subunit
Protein Kinase A
Catalytic subunit
Effects
Inositol Phospholipid Pathway
Phospholipase C
PIP2
DAG
PS
Protein Kinase C
G-protein
IP3
Ca++
Cellular Response
Intracellular Ca++
stores
Other Ca++
Dependent processes
1. Receptor / G-protein activate
phospholipase C
2. PLC catalyzes PIP2  IP3 and DAG
3. IP3  release of Ca++ from intracellular
stores (ER)
4. DAG (together with Ca++ and PS)
activate Protein Kinase C
Phosphatidylserine
Calcium as second messenger
Ca++
Guanylate kinase
GTP
Ca++
Intracellular Ca++
stores
cGMP
Neurotransmitter release
Muscle contraction
Protein Kinase C
Cam Kinase II
Protein Kinase G
Calcium / Calmodulin
Adenylate
cyclase
Metabolic
Enzymes
Pituitary gland
• Master gland
– Secretes 9 hormones that control other
glands
• 2 distinct parts
– Anterior pituitary (adenohypophysis)
– Posterior pituitary (neurohypophysis)
• Both parts controlled by neurosecretory
cells of the hypothalamus (part of the
brain!)
Neural Inputs
Hypothalamus
Portal Blood Vessels
Fig 9-15
Anterior Pituitary
-glandular tissue
Posterior Pituitary
Anterior Pituitary
Hypothalamus
Hormone 1
Portal blood vessels
Hormone 1
Target Tissue
Anterior Pituitary
Hormone 2
Posterior Pituitary
Hypothalamus
Hormone 1
Portal blood vessels
Target Tissue
Posterior Pituitary
• Neurosecretory neurons  Anterior Pituitary
– Secrete hormones into portal blood vessels
– Regulate secretion of other hormones from anterior
pituitary
• Neurosecretory neurons  Posterior Pituitary
– Secrete hormones directly into capillaries
Anterior Pituitary
• 2 hormone system
• 1st hormone stimulates or inhibits release
of other hormones from anterior pituitary
• 2nd hormone has effect on target tissue
Examples:
• 1st hormone
• 2nd hormone
– Corticotropin-releasing
hormone (CRH)
– Adrenocorticotropin
hormone (ACTH)
– Thyroid hormone
releasing hormone (TRH)
– Thyroid stimulating
hormone (TSH)
– Prolactin-inhibiting
hormone (PIH)
– Prolactin
Control of Anterior Pituitary
Hypothalmic Neurosecretory cells
Negative feedback
Releasing and release-inhibiting hormones
Anterior pituitary gland
Growth hormone
Non-endocrine Tissue
Metabolic response
ACTH
Thyroid Stimulating Hormone
Other Endocrine Tissue
Posterior Pituitary
•
•
Neurosecretory cells secrete hormones
directly onto capillaries
Only 2 hormones:
1. Antidiuretic hormone (ADH, also called
vasopressin)
•
Water retention by the kidney
2. Oxytocin
•
•
Uterine contractions during childbirth
Milk ejection during breast feeding
The Adrenal Glands
• An example of Pituitary control over other
endocrine tissue
• One gland attached to the top of each
kidney
Adrenal Medulla
Adrenal Cortex
Fig 9-32
Kidney
Adrenal Cortex
• Steroid hormones
– Aldosterone
– Cortisol
– Small amounts of
testosterone,
progesterone
Adrenal Medulla
• Catecholamine
– Epinipherine (adrenalin)
– Norepinipherine
(noradrenalin)
Control of Adrenal Cortex
Stress, circadian rhythm
and other neural input
Hypothalamic neurons
Corticotropin releasing hormone (CRH)
Anterior Pituitary
Adrenocorticotropic hormone (ACTH)
Adrenal cortex
Release of steroid hormones
Adrenal Cortical Steroids
• Mineralocorticoids
– eg. aldosterone
– Controls ion transport
in the kidney function
– Regulates expression
of a Na channel
– Important for water
reabsorption
• Glucocorticoids
– eg. cortisol
– Important for
metabolism esp. glucose
– Activate enzymes (in
liver) that increase
glucose production
–  blood glucose
Adrenal Medulla
• Catecholamines stored in large vesicles within
chromaffin cells of the adrenal medulla
• Chromaffin cells innervated by neurons of the
sympathetic nervous system
• ‘Fight or flight’ response
Sympathetic nerve terminal
Acetycholine synapse
Ca++
Adrenal medulla
Catecholamine
containing vesicles
Chromaffin cell
Blood vessel
• Ach depolarizes chromaffin cell by
activating nicotinic Ach receptors
• Opens voltage-gated Ca++ channels
• Ca++ causes fusion of vesicles
• Release of catecholamine into blood
stream
• Catecholamines released by adrenal
medulla:
– epinipherine 80%
– norepiniphrine 20%
– Also neurotransmitter
• Norepinephrine primary SNS
Effects of catecholamines depend
upon receptor type
• Activate adrenoreceptors
– Two types:  and 
1
Phospholipase C
IP3 & DAG
2
1
2
Adenylate cyclase
cAMP
Potential effects of catecholamine
receptor activation
• Heart
– , mediated  - contraction, HR
• Smooth Muscle (Blood vessels and lungs)
–  contraction
–  relaxation
• Metabolism
–  -  glycogenolysis  glucose
• Neural
–  -  K+ channel conductance
Some clinical stuff
•  adrenoreceptor agonists used to treat
asthma
•  blockers used to treat high blood
pressure
Summary
• Pituitary gland
– Hypothalamic control
– Anterior – 2 hormone system
– Posterior – direct hormone release into blood
stream
• Adrenal gland
– Cortex – steroid hormones
– Medulla - catecholamines
Blood Glucose Regulation
• Endocrine pancreas
– Only 2% of entire pancreas,
– the rest produces digestive enzymes
(exocrine)
– Islets of Langerhans
• Insulin ( cells)
• Glucagon ( cells)
• Somatostatin ( cells)
• Diabetes
– 2 million Canadians
– $9 billion per year health care costs
– Insulin isolated by Banting & Best 1922, U of T Dept of
Physiology (1923 Nobel Prize)
• Type 1
– No or very little insulin produced
• Type 2
– Reduced cellular response to insulin
• Consequences
–
–
–
–
Death
Blindness
Kidney disease
Limb amputation
Hormonal control of blood glucose
In the GI tract, 80% of all carbohydrate is digested to glucose
Basically:
Glucose
Used for ATP production
Glycogen
Used for glucose storage
Insulin
• Stimulus for secretion is high blood
glucose
• Secreted by  cells
• Leads to glucose uptake and storage in
liver, muscle and fat tissue.
• Effect is to  blood glucose
• Danger of Diabetes is hyperglycemia
Insulin Effects on Muscle and
Fat Tissue
• Insulin initiates transfer of glucose
transporters to cell membrane
•  blood glucose
•  production of glycogen
Effects in Muscle & Fat
Glycogen synthesis
Glucose
transporter
glucose
SNARE dependent
transport
Glucose
transporter
Insulin
storage
vesicle
In the Liver
• insulin stimulates the synthesis of an
enzyme (glucokinase)
• Required to ‘trap’ glucose in the cell
• initiates glycogen production
Effects in Liver
GLUT2
Glycogen synthesis
Glucose
transporter
glucose
X
glucose
Glucose 6-phosphate
glucokinase
‘trapped’
Other hormones
• Glucagon
– Secretion stimulated by low blood glucose
– Activates enzymes for gluconeogenesis and
glycogenolysis
– Leads to  blood glucose levels
• Somatostatin
– Regulates secretion of insulin and glucagon
Glucose Regulation Summary
• Endocrine pancreas
• Secretion of several hormones important
for blood glucose regulation
• Insulin  glucose uptake and storage
– Different effects on liver and muscle & fat
• Glucagon  glucose production
• Today
– Finish blood glucose
– Some words about the final
– Sample questions
Effects in Muscle & Fat
GLUT4
Glycogen synthesis
Glucose
transporter
glucose
SNARE dependent
transport
Glucose
transporter
Insulin
storage
vesicle
Insulin Effects on Muscle and
Fat Tissue
• Insulin initiates transfer of glucose
transporters to cell membrane
•  blood glucose
•  production of glycogen
In the Liver
• insulin stimulates the synthesis of an
enzyme (glucokinase)
• Required to ‘trap’ glucose in the cell
• initiates glycogen production
Effects in Liver
GLUT2
Glycogen synthesis
Glucose
transporter
glucose
X
glucose
Glucose 6-phosphate
glucokinase
‘trapped’
Other hormones
• Glucagon
– Secretion stimulated by low blood glucose
– Activates enzymes for gluconeogenesis and
glycogenolysis
– Leads to  blood glucose levels
• Somatostatin
– Regulates secretion of insulin and glucagon
Glucose Regulation Summary
• Endocrine pancreas & cell type
• Secretion of several hormones important
for blood glucose regulation
• Insulin  glucose uptake and storage
– Different effects on liver and muscle & fat
• Glucagon  glucose production